Abstract 16396: Glucose-6-Phosphate Dehydrogenase Deficiency Promotes Susceptibility to Pressure Overload Induced Left Ventricular Dysfunction and Hypertrophy
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymopathy in the world, is highly prevelant in Africans, and has been associated with either increased or reduced risk for cardiovascular disease. G6PD determines the cytosolic NADPH concentration and facilitates the removal of ROS via the glutathione pathway. We previously found that high sugar diets exaccerabate pathological cardiac hypertrophy in response to pressure overload, which was prevented by antioxidant treatment. Because high frucose intake increases myocardial ROS formation, and NADPH concentration affects ROS removal, we hypothesized that G6PD deficiency would exacerbate pathological hypertrophy in response to pressure overload with a high fructose diet. G6PD deficient mice (G6PDX) with 20% residual G6PD activity (which mimics the common human enzymopathy) and WT mice were subjected to pressure overload induced by transverse aortic constriciton (TAC) and fed either a high starch or a high fructose diet (n=12-16/group). After 16 weeks, G6PDX and WT mice had similar LV hypertrophy and ejection fraction in response to TAC when fed the starch diet (data not shown). On the other hand, fructose-fed mice showed a significant effect of G6PD deficiency, with a lower LV ejection fraction and greater cardiac hypertrophy in response to TAC in G6PDX vs WT mice (Figure). No differences were observed in body mass or tibia length. These results indicate that G6PD deficiency enhanced susceptability to LV hypertrophy in response to combined pressure-overload and high fructose intake. These finding suggest that investigation into the effects of dietary sugar intake on cardiovascular disease in G6PD deficient people is warrented.
- © 2011 by American Heart Association, Inc.